Smoking-mediated nicotinic acetylcholine receptors (nAChRs) for predicting outcomes for head and neck squamous cell carcinomas

Abstract

Background As a human tumor disease, head and neck squamous cell carcinoma (HNSCC) is associated with a high mortality rate worldwide. Nicotinic acetylcholine receptors (nAChRs) are transmembrane receptor proteins and exert their biological effects following activation by nicotine. We aimed to construct a prognostic signature based on the expression of nAChRs among smokers with HNSCC. Methods The transcriptome profile of nAChRs was obtained from The Cancer Genome Atlas (TCGA). Following the integration of survival information, univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analyses were performed to screen the prognosis-related nAChRs and construct a prognostic signature. Kaplan–Meier (KM), receiver operating characteristic (ROC), principal component analysis (PCA), and independent prognostic analysis were utilized to verify the predictive power of the nAChR-associated prognostic signature. The expression of α5 nAChR in clinical samples was verified by quantitative reverse transcriptase PCR. Results Subunits α2, α5, α9, and β4 were related to the prognosis. The prognostic signature comprised the expression of subunits α5, α9, and β4. The nAChR-associated signature showed high sensitivity and specificity for prognostic prediction and was an independent factor for overall survival. Based on the clinical variables and expression of nAChRs, a nomogram was constructed for predicting the outcomes of HNSCC patients who were smokers in the clinical settings. In clinical specimens, α5 nAChR showed high expression in HNSCC tissues, especially among smokers. Conclusions The nAChR-associated signature constructed in this study may provide a better system for the classification of HNSCC patients and facilitate personalized treatment according to their smoking habits.

The expression of nicotinic acetylcholine receptor subunits and their associations with local immune cells and prognosis in oral squamous cell carcinoma

“…30 Elevated α5 in OSCC may indicate increased EMT phenotypes and decreased cancer-killing immune cells in the TME, both of which are associated with a worse prognosis in many cancers. 26,27,30 On the contrary, though previous study demonstrated that α7-nAChRs in OSCC cell lines are involved in nicotine-mediated cell survival and cisplatin resistance, 45 the α7 expression level was found to have insignificant survival influence in HNC patients, 46 which is consonant with our study.…”

Editorial: Molecular landscapes of human papillomavirus-related squamous cell carcinoma

“…As an emerging technological tool, data mining has been widely applied in the field of medicine. It can assist researchers in extracting valuable information from massive data, such as identifying the pathogenesis of cancer ( 6 ), recognizing patients’ risk factors ( 7 ), and predicting prognosis ( 8 ). Additionally, data mining can help discover novel treatment strategies and drugs, as well as optimize existing treatment regimens.…”